Toll-like receptors (TLRs) have a key role in innate immunity. These receptors recognize both pathogen-associated molecular patterns and molecules that are released from damaged tissue. TLRs mediate signal transduction pathways through the activation of transcription factors that regulate the expression of proinflammatory cytokines and chemokines and are required for the development of adaptive immune responses. TLRs might have an important role in the pathogenesis of renal diseases: their exaggerated activation is associated with ischemic kidney damage, acute kidney injury, end-stage renal failure, acute tubulointerstitial nephritis, acute renal transplant rejection and delayed allograft function. As the results of previous studies concerning the role of TLRs in renal diseases are conflicting, further work is needed to determine the exact role of these receptors and to evaluate strategies to prevent TLR-mediated local inflammation. This Review discusses the evidence supporting a role for TLRs in contrasting bacterial infections and in causing or aggravating renal conditions when TLR activation leads to a harmful inflammatory response.

BackgroundChronic kidney disease (CKD) is becoming a serious health problem; the number of people with impaired renal function is rapidly rising, especially in industrialized countries. A major complication of CKD is cardiovascular disease. Accelerated atherosclerosis has been observed in early stages of renal dysfunction. The purpose of this study was to examine the relationship between the degree of renal insufficiency and both the prevalence and intensity of coronary artery disease (assessed on the basis of number of vessels with stenosis).Methods446 individuals with both serum creatinine >120 μmol/l (men) or >96 μmol/l (women) and acute coronary syndrome were included in the study. All patients included in this analysis underwent urgent coronarography. Data concerning glomerular filtration rate (GFR), number of vessels with stenosis, hypertension, lipid disorders, creatinine concentration, C-reactive protein, glucose and lipid profile were analyzed.ResultsThis study confirmed that moderate to severe renal impairment is associated with accelerated atherosclerosis. Moreover, patients with GFR values below 60 ml/min/1.73 m2 are predisposed to accelerated, multivessel cardiovascular disease.ConclusionsGFR seems to be an independent risk factor for multivessel cardiovascular disease. Due to the fact that patients with renal dysfunction are at high risk of cardiovascular events, they should obtain optimal treatment resulting not only in kidney protection but also in the elimination of cardiovascular risk factors.

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IntroductionIn chronic kidney disease (CKD) patients left ventricular (LV) diastolic dysfunction occurs frequently and is associated with heart failure (HF) and higher mortality. Left ventricular systolic dysfunction is associated with coronary artery disease (CAD) and is a major determinant of prognosis. The aim of this study was to assess indices of LV diastolic dysfunction in CKD patients.Material and methodsStudy included 118 CKD patients. All patients underwent transthoracic echocardiography. Diastolic function based on E and A, E/A ratio and pulmonary vein flow velocities as well as EF%, deceleration time, RA, LA volume were assessed. In dialysis patients examination was carried out before and after dialysis.ResultsIn CKD patients the stage of renal failure was associated with the significant increase in LV mass (268.0 ±47.6 CKD I/II vs. 432.7 ±122.4 CKD V/dialysis, p < 0.0001), systolic LV (37.3 ±4.5 vs. 51.2 ±8.9, p < 0.0001) and diastolic LV (CKD I–II 44.7 ±4.1 vs. CKD III 48.5 ±6.7 vs. CKD IV 47.1 ±5.6; p = 0.004) dimensions and in the size of the LA (40.4 ±2.0 vs. 41.9 ±2.7 vs. 42.3 ±3.2 vs. 44.8 ±3.1; p < 0.0001). The increase the E/E’ ratio between groups of patients (6.7 ±1.5 vs. 8.9 ±2.4 vs. 11.5 ±4.0 vs. 13.5 ±5.0; p < 0.0001) was seen in this study. The reduction in deceleration time (247.2 ±34.5 in CKD I/II vs. 197.4 ±61.0 in CKD IV, p = 0.0005) along with the decrease in estimated glomerular filtration rate was also observed in this study.ConclusionsEarly identification of factors involved is necessary to prevent this devastating process. Many indexes of contractility are used and each of them has imperfections. It seems that TVI, E, E/A and E/E’ are good instruments for the early detection of left ventricular hypertrophy and diastolic dysfunction.

Biomarkers should have high sensitivity, specificity, reproducibility, be cost-effective, and provide incremental predictive or diagnostic utility over standard risk factors or tests. Despite numerous studies investigating biomarkers in heart failure (HF), there are only a few that predict HF in hypertensive patients. This article summarizes data from numerous studies concerning possible biomarkers of HF in hypertensive patients such as: serum uric acid (SUA), interleukins, monocyte chemoattractant protein one (MCP-1), cardiotrophin-1 (CT-1), carboxy-terminal propeptide of procollagen type I (PICP), type I collagen telopeptide (CITP) and N-terminal propeptide of type III procollagen (PIIINP), metalloproteinases (MMPs), B-type natriuretic peptide (BNP) and its derivatives, glycoprotein CA125 and cystatin C. Early detection of patients of increased risk of hypertensive heart disease may result in early implementation of effective preventive strategies. Therefore, there is need to identify newer biomarkers, if they can improve risk prediction, identifying patients, in which earlier or more aggressive intervention will improve clinical outcomes.

Despite positive effects on the plasma lipid profile and vascular events, statin use is associated with various side effects. Among these, statins might cause a disruption of a number of regulatory pathways including insulin signaling. This may affect insulin sensitivity, pancreatic beta-cell function and adipokine secretion. The statin-associated risk of new-onset diabetes (NOD) appears to be a dose-dependent class effect. It still remains unclear whether statin treatment is associated with increased risk of NOD in the general population or if there are groups of individuals at particular risk. However, according to the available data it seems that cardiovascular (CV) benefits in high-risk individuals strongly favor statin therapy since it outweighs other risks. Whether statins should be used for primary prevention among patients with a relatively low baseline CV risk is still questionable, however the results of primary prevention trials have shown reductions in mortality in this population. Thus, there is a need for randomized, placebo-controlled statin studies with carefully selected groups of patients and NOD as a key end point in order to resolve queries concerning this issue.

Paraoxonases (PONs) may exert anti-atherogenic action by reducing lipid peroxidation. We evaluated the influence of 2 polymorphisms within PON1 (192 Gln/ Arg) and PON2 (311 Ser/Cys) genes in 407 young Poles: 273 patients who experienced a first myocardial infarction (MI) under the age of 45 (study group) and 134 healthy volunteers (control group) with a HEART Score < or =2 (low risk). Paraoxonase 1 polymorphism 192Gln/Arg influenced the risk of premature MI (P = .0054). A positive family history of coronary artery disease (CAD) was associated with the 192Arg allele (P = .0107). The association between PON1 genotype (192 Gln/Arg) and low-density lipoprotein cholesterol (LDL-C) (P = .036) levels was also observed. However, we did not find any relationship between polymorphism 311Ser/Cys and CAD risk (P = .418). PON1 polymorphism 192Gln/Arg influenced the risk of premature MI. The association between PON1 genotype (192 Gln/Arg) and serum LDL-C levels may be explained by PON participation in reverse cholesterol transport.

At present, it is difficult to unequivocally assess the impact of statins on blood pressure. However, according to most authors, the impact of statins on the decrease in BP is slight, but significant, especially among patients with hypertension.